Resumen

The purposes of this study are to evaluate the treatment effect of seladelpar on composite biochemical improvement in cholestasis markers based on ALP and total bilirubin and to evaluate the safety of seladelpar over 12 months of treatment compared to placebo. The study also checked the effect of treatment on the symptoms of PBC, including pruritus.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 75 YearsSexo: ALL

Criterios de inclusión

Must have given written informed consent (signed and dated) and any authorizations required by local law.
Male or female with a definitive diagnosis of primary biliary cholangitis (PBC).
Ursodeoxycholic acid (UDCA) for the past 12 months (stable dose for \>3 months prior to screening) or intolerant to UDCA (last dose of UDCA \>3 months prior to screening).
Laboratory parameters measured by the Central Laboratory at screening:
Alkaline phosphatase (ALP) ≥1.67× ULN (upper limit of normal)
Aspartate aminotransferase (AST) ≤3× ULN
Alanine aminotransferase (ALT) ≤3× ULN
Total bilirubin ≤2× ULN
Estimated glomerular filtration rate (eGFR) \>45 mL/min/1.73 m\^2 (calculated by the Modification of Diet in Renal Disease study equation).
International normalized ratio (INR) below 1.1× ULN (For individuals on anticoagulation therapy, INR must be maintained in the range required for prophylaxis for their specific disease).
Platelet count ≥100 ×10\^3/µL.
Females of reproductive potential must use at least 1 barrier contraceptive and a second effective birth control method during the study and for at least 90 days after the last dose. Male individuals who are sexually active with female partners of reproductive potential must use barrier contraception, and their female partners must use a second effective birth control method during the study and for at least 90 days after the last dose.

Criterios de exclusión

Previous exposure to seladelpar (MBX-8025).
A medical condition other than PBC that, in the investigator's opinion, would preclude full participation in the study (e.g., cancer) or confound its results (e.g., Paget's disease, any active infection).
Advanced PBC as defined by the Rotterdam criteria (albumin below the lower limit of normal and total bilirubin above 1.0 × ULN).
Presence of clinically important hepatic decompensation, including the following:
History of liver transplantation, current placement on liver transplantation list, or current Model for End-Stage Liver Disease (MELD) score ≥12. For individuals on anticoagulation medication, evaluation of the baseline INR, in concert with their current dose adjustments of their anticoagulant medication, will be taken into account when calculating the MELD score. This will be done in consultation with the medical monitor.
Complications of portal hypertension, including known esophageal varices, history of variceal bleeds or related interventions (e.g., transjugular intrahepatic portosystemic shunt placement), ascites, and hepatic encephalopathy.
Cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis, hepatocellular carcinoma, or hepatorenal syndrome.
Other chronic liver diseases:
Current features of autoimmune hepatitis (AIH) as determined by the investigator based on immunoserology, liver biochemistry, or historic confirmed liver histology.
PSC determined by the presence of diagnostic cholangiographic findings.
History or clinical evidence of alcoholic liver disease.
History or clinical evidence of alpha-1-antitrypsin deficiency.
History of biopsy confirmed nonalcoholic steatohepatitis (NASH).
History or evidence of Gilbert's syndrome with elevated total bilirubin.
History or evidence of hemochromatosis.
Hepatitis B, defined as the presence of hepatitis B surface antigen.
Hepatitis C, defined as the presence of hepatitis C virus ribonucleic acid.
History, evidence, or high suspicion of hepatobiliary malignancy based on imaging, screening laboratory values, and/or clinical symptoms.
Known history of human immunodeficiency virus (HIV) or positive antibody test at screening
Clinically important alcohol consumption, defined as more than 2 drink units per day (equivalent to 20 g) in women and 3 drink units per day (equivalent to 30 g) in men, or inability to quantify alcohol intake reliably.
History of malignancy diagnosed or treated, actively or within 2 years, or ongoing evaluation for malignancy; localized treatment of squamous or noninvasive basal cell skin cancers and cervical carcinoma in situ is allowed if appropriately treated prior to screening.
Treatment with obeticholic acid (OCA) or fibrates (e.g., bezafibrate, fenofibrate, elafibranor, lanifibranor, pemafibrate, saroglitizar) 6 weeks prior to screening.
Treatment with colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (\>2 weeks) during 2 months prior to screening
Treatment with anti-pruritic drugs (e.g., cholestyramine, naltrexone, rifampicin, sertraline, or any experimental approach) must be on a stable dose within 1 month prior to screening
Treatment with any other investigational therapy or device within 30 days or within 5 half-lives, whichever is longer, prior to screening
For females, pregnancy or breastfeeding.
Any other condition(s) that would compromise the safety of the individual or compromise the quality of the clinical study, as judged by the investigator.
Immunosuppressant therapies.
Other medications that effect liver or gastrointestinal (GI) functions, such as absorption of medications or the roux-en-y gastric bypass procedure, may be prohibited and should be discussed with the medical monitor on a case-by-case basis.
Active Coronavirus Disease-2019 (COVID-19) infection during Screening.

Intervenciones

drug

Seladelpar 10 mg

Seladelpar 10 mg one capsule daily for double-blind period, for a duration of up to 12 months

drug

Placebo

One capsule daily for double-blind period, for a duration of up to 12 months

drug

Seladelpar 5 mg

If down-titration needed, one capsule daily for double-blind period, for a duration of up to 12 months

Ubicaciones

Centro Medico Dra. De Salvo

CABA, Buenos Aires, Argentina

STAT Research S.A.

Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina

Hospital Italiano de La Plata

La Plata, Buenos Aires, Argentina

DIM CliniaPrivada

Ramos Mejía, Buenos Aires, Argentina

CINME (Centro de Investigaciones Metabolicas)

Buenos Aires, Argentina

Hospital Italiano de Buenos Aires

Caba, Argentina

RESPONSE: A Placebo-controlled, Randomized, Phase 3 Study to Evaluate the Efficacy and Safety of Seladelpar in Patients With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA)

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Seladelpar 10 mg

Placebo

Seladelpar 5 mg

Ubicaciones

Centro Medico Dra. De Salvo

STAT Research S.A.

Hospital Italiano de La Plata

DIM CliniaPrivada

CINME (Centro de Investigaciones Metabolicas)

Hospital Italiano de Buenos Aires

Patrocinadores